To investigate numerical aberrations of chromosome 17 and the p53 locus in early stages of hepatocellular carcinoma (HCC), 12 fresh-frozen specimens of small HCCs (less than 30 mm in size) were examined by dual-color fluorescence in situ hybridization. We used a chromosome 17 alpha-satellite DNA probe and a p53 locus-specific DNA probe. We also performed immunohistochemical analysis for p53 protein in the same cases. Gain of chromosome 17 was the most frequently observed anomaly, present in 58% of cases, and deletion of the p53 locus was observed in 50% of cases. The combination of chromosome 17 gain and p53 locus deletion was observed in 33.3% of cases. However, overexpression of p53 protein was not observed in any specimens. Our results suggest that gain of chromosome 17 and deletion of the p53 locus could represent early genetic events, prior to overexpression of p53 protein due to mutation, in early stage HCC.